First Mesenchymal Stromal Cell Therapy Approved for Graft-versus-Host Disease

On Dec. 18, 2024, the US Food and Drug Administration (FDA) approved Ryoncil^® (remestemcel-L-rknd) for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) in pediatric patients two months of age and older. Ryoncil is a mesenchymal stromal cell (MSC) therapy, providing off-the-shelf stem cells from the bone marrow of an unrelated, healthy donor that can boost the anti-inflammatory response. This marks the first MSC therapy approved and the first therapy for children under 12 years of age with steroid-refractory acute GVHD, a disease with high mortality. The recommended dose is two million cells/kg body weight per intravenous (IV) infusion given twice per week, at least three days apart, for four consecutive weeks. The launch date is currently not known. It is expected to be available at transplant centers and other treating hospitals. Full prescribing information may be found here.

At a Glance

• Brand Drug: Ryoncil(remestemcel-L-rknd)
• Manufacturer: Mesoblast
• Date Approved: Dec. 18, 2024
• Indication:  For the treatment of steroid-refractory acute GVHD disease in pediatric patients two months of age and older
• Dosage Forms Available: Cell suspension for IV infusion in a target concentration of 6.68 X 10⁶ MSCs per mL in 3.8mL contained in a 6mL cryovial
• Launch Date: The launch date is not known at this time.
• Estimated Annual Cost: Cost is not known at this time.
• FDA Designation(s): Orphan Drug. Fast Track. Priority Review.
• Acute GVHD is the main complication of Hematopoietic Stem Cell Transplantation (HSCT) and is the major cause of morbidity and mortality in this setting. In HSCT, patients receive stem cells from a healthy donor to form new healthy blood cells as part of treatment for certain types of blood cancers or disorders. In patients receiving HSCT, about 50% develop acute GVHD, which is when the immune cells produced by the donor react against their host. First-line treatment is steroid therapy; however, around half of the patients with acute GVHD do not respond to initial steroid treatment and are left with few therapeutic options.
• In the US, approximately 4,500 allogeneic transplants are performed annually in children with refractory hematological malignancies or life-threatening genetic diseases under the age of 20, and between 1,300 and 2,250 of these children will develop acute GVHD.
• Ryoncil is made from culture-expanded MSC derived from the bone marrow of an unrelated donor. It is believed to have immunomodulatory properties to counteract the inflammatory processes that are implicated in steroid-refractory acute GVHD by downregulating the production of pro-inflammatory cytokines, increasing the production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.
• After two complete response letters citing the need for more data, this approval is supported by Mesoblast’s pivotal Phase III, multicenter, single-arm, open-label trial that enrolled 54 children. Ryoncil had an overall response of 70% in pediatric patients at Day 28 including 30% of children that had a complete response. The overall survival was 74% on Day 100 and 69% on Day 180. A four-year observational survival study of children showed that overall survival in the Ryoncil cohort was 63% at one year, 51% at two years, and 49% at four years.
• The most common adverse events are infections, fever, hemorrhage, edema, abdominal pain, and hypertension. Patients should be monitored for hypersensitivity or acute infusion reactions during treatment, with discontinuation recommended if dyspnea, hypotension, fever, tachycardia, cyanosis, or hypoxia are observed. Premedication with corticosteroids and antihistamines is required prior to infusion.
• Jakafi^® (ruxolitinib – Incyte) is approved for steroid-refractory acute GVHD in patients over 12 years of age. There are currently no FDA-approved treatments in the US for children under 12 with steroid-refractory acute GVHD.
• Mesoblast has plans to study Ryoncil in larger populations of adults with acute GVHD. Cynata Therapeutics is in Phase II studies for CYP-001, a two-dose MSC therapy with results expected end of 2025. ASC Therapeutics is investigating an off-the-shelf Decidua Stromal Cells (DSC) IV option for steroid-refractory acute GVHD. Phase II results are expected in April 2026.